• Clinical and Experimental Pediatrics
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• 제57권2호
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• pp.91-95
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• 2014

Griscelli syndrome type 2 (GS2) is a rare autosomal recessive disease caused by mutations in the RAB27A gene. It is characterized by cutaneous hypopigmentation, immunodeficiency, and hemophagocytic lymphohistiocytosis. We describe 2 brothers who had GS2 with clinically diverse manifestations. The elder brother presented with a purely neurological picture, whereas the younger one presented with fever, pancytopenia, hepatosplenomegaly, and erythema nodosum. Considering that cutaneous hypopigmentation was a common feature between the brothers, genetic analysis for Griscelli syndrome was performed. As the elder sibling had died, mutation analysis was only performed on the younger sibling, which revealed a novel homozygous mutation in the RAB27A gene on chromosome 15 showing a single-base substitution (c.136T>A p.F46I). Both parents were heterozygous for the same mutation. This confirmed the diagnosis of GS2 in the accelerated phase in both siblings. The atypical features of GS2 in these cases are a novel mutation, isolated neurological involvement in one sibling, association with erythema nodosum, and 2 distinct clinical presentations in siblings with the same genetic mutation.

• Asian Pacific Journal of Cancer Prevention
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• 제15권5호
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• pp.2027-2033
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• 2014

Background: We aimed to assess RET proto-oncogene polymorphisms in three different Iranian families with medullary thyroid cancer (MTC), and performed molecular dynamics simulations and free energy stability analysis of these mutations. Materials and Methods: This study consisted of 48 patients and their first-degree relatives with MTC confirmed by pathologic diagnosis and surgery. We performed molecular dynamics simulations and free energy stability analysis of mutations, and docking evaluation of known RET proto-oncogene inhibitors, including ZD-6474 and ponatinib, with wild-type and mutant forms. Results: The first family consisted of 27 people from four generations, in which nine had the C.G2901A (P.C634Y) mutation; the second family consisted of six people, of whom three had the C.G2901T (P.C634F) mutation, and the third family, who included 12 individuals from three generations, three having the C.G2251A (P.G691S) mutation. The automated 3D structure of RET protein was predicted using I-TASSER, and validated by various protein model verification programs that showed more than 96.3% of the residues in favored and allowed regions. The predicted instability indices of the mutated structures were greater than 40, which reveals that mutated RET protein is less thermo-stable compared to the wild-type form (35.4). Conclusions: Simultaneous study of the cancer mutations using both in silico and medical genetic procedures, as well as onco-protein inhibitor binding considering mutation-induced drug resistance, may help in better overcoming chemotherapy resistance and designing innovative drugs.

• 대한유전성대사질환학회지
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• 제13권2호
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• pp.98-103
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• 2013

Purpose: MAT-I/III deficiency by MAT1A gene mutation causes isolated hypermethioninemia, which is considered to be a clinically benign disease. But in some patients, mental retardation, developmental delay, myelination disorder may be shown. This study was performed to find out the clinical manifestations and genetic characteristics of patients with isolated hypermethioninemia. Methods: Clinical, biochemical and genetic analysis were done to 10 patients with isolated hypermethioninemia who were referred to department of pediatrics, Soonchunhyang University Hospital from March 1999 to March 2012. Results: At first visit, all patients' mean plasma methionine level was 5.5 mg/dL (2.1-14.6) and there were no increase of amino acid levels including homocystine in all patients. Serum homocysteine level was evaluated in seven patients who visited after year 2003, and ranged from 4.96 to $11.15{\mu}mol/L$ (normal < $25{\mu}mol/L$). Methionine restricted diet was started to all patients. Nine patients who managed regularly showed normal development, but one patient whose initial plasma methionine level was 14.6 mg/dL showed language delay at 1 year of age and was diagnosed as mild mental retardation (IQ=66) at 6 years of age. Genetic analysis was done to eight patients, R264H mutation was identified in seven patients. Also, both R299C and R356Q mutation were identified in one patient. Conclusion: Clinical findings in patients with isolated hypermethioninemia were generally good, but one patient showed mental retardation and language difficulty. R264H mutation which usually inherits as an autosomal dominant trait was most frequently found in our patients, and R299C/R356Q mutation were also identified.

• Journal of Microbiology
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• 제34권2호
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• pp.158-165
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• 1996

The signal transduction pathways through the RAS gene product and adenyl cyclease play a critical role in regulation of the cell cycle in yeast, Saccharomyces cerevisiae. We examined the genetic relationship between the spt3 gene and ras/cAMP pathway. A mutation in the SPT3 gene suppressed cell cycle arrest at the G1 phase caused by either an inactivation of the RAS or CYR1 gene which encodes a yeast homologue of human ras proto-oncogene or adenyl cyclase, respectively. The phenotypes such as sporulation and heat shock resistancy, that resulted from a partial inactivation of the RAS or CYR1 genes, were also suppressed by the spt3 mutation. Expression of the SSA1 gene encoding one of th heat shock proteins (Hsp70) can be induced by heat shock or nitrogen starvation. Expression of this gene is derepressed in cry1-2 and spt3 mutants. The bcy 1 mutation repressed by the bcy1 mutation, but not in spt3 mutants. These results suggest that the SPT gene is involved in expression of genes that are affected by the RAS/cAMP pathway.

• 대한기계학회:학술대회논문집
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• 대한기계학회 2000년도 춘계학술대회논문집A
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• pp.725-730
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• 2000

Genetic algorithms based on the theory of natural selection, have been applied to many different fields, and have proven to be relatively robust means to search for global optimum and handle discontinuous or even discrete data. Genetic algorithms are widely used for unconstrained optimization problems. However, their application to constrained optimization problems remains unsettled. The most prevalent technique for coping with infeasible solutions is to penalize a population member for constraint violation. But, the weighting of a penalty for a particular problem constraint is usually determined in the heuristic way. Therefore this paper proposes, the effective technique for handling constraints, the ranking penalty method and hybrid genetic algorithms. And this paper proposes dynamic mutation tate to maintain the diversity in population. The effectiveness of the proposed algorithm is tested on several test problems and results are discussed.

• 지능정보연구
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• 제8권2호
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• pp.189-203
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• 2002

이 논문에서 우리는 유전알고리즘의 적응적 연산자에 대한 수행도를 비교한다. 이러한 적응적 연산자를 위해서, 유전알고리즘의 교차변이와 돌연변이 연산자가 고려되어 지며, 이 논문에서 개발된 하나의 퍼지로직 제어기와 기존연구에서 사용된 두개의 휴리스틱 기법이 제시되어진다. 이러한 퍼지로직 제어기와 두개의 기존 휴리스틱 기법들은 유전 탐색과정 동안에 그 연산자의 비율들을 적응적으로 조절한다. 이 논문에서 제시된 모든 알고리즘들은 수치예제에서 분석되어 지며, 결론적으로 이들 알고리즘 중에서 최적의 알고리즘이 추천된다.

• Journal of Genetic Medicine
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• 제3권1호
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• pp.15-19
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• 1999

We have investigated the genetic variation in the human apo B mRNA editing protein (apobec-1) gene. Exon 3 of the apobec-1 gene was amplified by polymerase chain reaction. After detection of an additional band by single strand conformational polymorphism (SSCP) analysis, sequencing of the SSCP-shift sample revealed a single-base mutation. The mutation was a CGG transversion at codon 80 resulting in a lleRMet substitution. This substitution was confirmed by restriction fragment length polymorphism analysis since a Pvull site is abolished by the substitution. Population and family studies confirmed that the inheritance of the genotypes for apobec-1 gene polymorphism is controlled by two codominant alleles (P1 and P2). A significant difference in plasma triglyceride was detected among the different apobec-1 genotypes in the CAD patients (P<0.05). Our study could provide the basis for elucidating the interaction between genetic variation of the apobec-1 gene and disorders related to lipid metabolism.

• 산업경영시스템학회지
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• 제28권3호
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• pp.149-155
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• 2005

In this paper, we optimize simulation model of a manufacturing system using the real-coded genetic algorithm. Because the manufacturing system expressed by simulation model has stochastic process, the objective functions such as the throughput of a manufacturing system or the resource utilization are not optimized by simulation itself. So, in order to solve it, we apply optimization methods such as a genetic algorithm to simulation method. Especially, the genetic algorithm is known to more effective method than other methods to find global optimum, because the genetic algorithm uses entity pools to find the optimum. In this study, therefore, we apply the real-coded genetic algorithm to simulation optimization of a manufacturing system, which is known to more effective method than the binary-coded genetic algorithm when we optimize the constraint problems. We use the reproduction operator of the applied real-coded genetic algorithm as technique of the remainder stochastic sample with replacement and the crossover operator as the technique of simple crossover. Also, we use the mutation operator as the technique of the dynamic mutation that configures the searching area with generations.

• 정보처리학회논문지D
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• 제8D권1호
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• pp.81-86
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• 2001

소프트웨어 테스팅의 중요 목표 중의 하나는 '좋은' 테스트 데이터 집합을 생성하는 것으로 이는 매우 어렵고 시간이 걸리는 작업이다. 본 논문은 소프트웨어 테스팅을 위한 자동 테스트 데이터 집합 생성에 유전자 알고리즘을 적용하는 방법을 제시하며 자동 테스트 데이터 생성에서 유전자 알고리즘의 효용성을 보이기 위해 유테이션 테스팅을 도입한다. 본 연구는 테스트 데이터 생성 과정이 테스트 대상 프로그램의 구현에 대한 지식을 필요로하지 않는다는 점에서 다른 방법들과 다르다. 또한, 제안된 방법의 효율성을 보이기 위하여 몇 가지 실험을 통해서 블랙박스 테스트 생성 기법은 랜덤 테스팅과 비교한다.

• 한국공간구조학회논문집
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• 제5권3호
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• pp.117-122
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• 2005

This paper investigated the optimum design of truss structures based on Genetic Algorithms (GA's). With GA's characteristic of running side by side, the overall optimization and feasible operation, the optimum design model of truss structures was established. Elite models were used to assure that the best units of the previous generation had access to the evolution of current generation. Using of non-uniformity mutation brought the obvious mutation at earlier stage and stable mutation in the later stage; this benefited the convergence of units to the best result. In addition, to avoid GA's drawback of converging to local optimization easily, by the limit value of each variable was changed respectively and the genetic operation was performed two times, so the program could work more efficiently and obtained more precise results. Finally, by simulating evolution process of nature biology of a kind self-organize, self-organize, artificial intelligence, this paper established continuous structural optimization model for ten bars cantilever truss, and obtained satisfactory result of optimum design. This paper further explained that structural optimization is practicable with GA's, and provided the theoretic basis for the GA's optimum design of structural engineering.